This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Active proton transport mechanisms establish and maintain a luminal acidic environment in the excurrent ducts of the male reproductive tract. The low luminal pH and a low bicarbonate concentration are important for sperm maturation, the prevention of premature activation of acrosomal enzymes, and for maintaining sperm in a quiescent state during storage in this organ. Despite this critical function in male reproductive physiology, acidification processes in the male reproductive tract are still incompletely understood. Our laboratory is studying the mechanisms that participate in luminal acidification and its regulation in the epididymis and vas deferens. The ultimate goals of this study are to understand how defective acidification may impair reproductive function in pathologic states, and how intervention to manipulate acidification may eventually be used to control male fertility. The non-invasive self-referencing proton-selective micro electrode developed in the BioCurrrents Research Center has allowed us to identify the major proton secretory mechanism in the initial part of the vas deferens. In collaboration with Peter Smith, we have shown that a bafilomycin-sensitive, vacuolar proton-pumping H+-ATPase (V-ATPase) is concentrated in the apical membrane of a subpopulation of epithelial cells (clear cells) and is a major contributor to luminal acidification. In acidifying clear cells, proton secretion is regulated via recycling of V-ATPase-containing vesicles to and from the plasma membrane. .